Core D provides cutting edge genomic and proteomic tools to the members of the Program. CSHL has made a very substantial institutional commitment during the last funding cycle to development of a large next-generation sequencing facility, and has considerable capacity provided by four HiSeq and twelve llx lllumina sequencers, along with sequencing machines from Pacific BioSciences and 454. Enabled by this Core D provides as extensive set of next-generation sequencing tools applications for Program Project members. This includes RNA-Seq ,Chip-Seq and innovative DNA methylome analysis tools. In addition. Core D will allow program members to perform copy-number variation (CfvIV) and single-nucleotide variation (SNV) and other mutational analysis with the next-generation sequencing tools. In addition the Core will aid investigators in de-convolution of multiplexed shRNA screens. Core D will also enable projects that utilize next-generation sequencing technologies for analyzing DNA or RNA at the single-cell level. Core D also performs real-time PCR analysis with TaqMan and microarray services. Core D employs a world leader in the field of proteomics. Dr. Darryl Pappin. Specific services include quantitative proteome profiling using SILAC or iTRAQ, analysis of the protein content of multiprotein complexes, and analysis of post-translational modifications. Core D also provides a dedicated computational scientist who will provide Program Project members with expert analysis of the high-throughput genomic and proteomic data generated by Core D. Custom tools will be developed for Program Project members where needed. Finally, Core D acquires human tumor samples and human cancer cell lines for Program Project members from available public sources including the Cooperative Human Tissue Network and isolates DNA, RNA, or protein as needed